Idiopathic clubfoot is one of the most common deformities of the musculoskeletal system. This disorder occurs in 1/1000 live births and requires extensive and expensive treatment. No treated feet are normal and a significant number of poor results occur with attendant life-long disability. The cause of isolated clubfoot is unknown. Extensive anatomic and epidemiologic studies have failed to clarify our understanding of this disorder. Recent complex segregation analyses support the concept that a single major gene contributes significantly to the likelihood of having clubfoot in many or most people with the clubfoot phenotype. This project seeks to localize and identify the gene or genes causing idiopathic clubfoot. The entire genome will be screened in two large families by using DNA pooling and shared segment analysis to rapidly identify a susceptibility locus (loci) in these two families. Affected pedigree member analysis will be used to determine if the locus or loci found in the two large families are linked to the clubfoot phenotype in sib pairs/affected pedigree members sets. All individuals with idiopathic clubfoot will be studied, regardless of family history using population based population based association studies to determine the extent to which the locus(i) segregate with the clubfoot phenotype in singleton families. Promising loci will be investigated by positional cloning techniques and recently available candidate gene maps.